Abstract 005: Involvement of Decreases in Regulatory T Cells and Splenic Sympathetic Nerve in the Development of Hypertension in Genetically Hypertensive Rats

Abstract

Background: Autonomic nervous system can modulate immune system thereby influences the pathogenesis of hypertension. Among the immune cells, activated T cells have been implicated in the genesis of hypertension. In contrast, regulatory T cells (Treg cells), which maintain immune homeostasis, are reported to prevent AngII-induced hypertension. However, there are few studies of Treg cells in spontaneously hypertensive models. In particular, the spleen is an important organ to regulate immune system and splenic nerve can modulate immune responses in the spleen. Here, we investigated the role of Treg cells in hypertension and the involvement of splenic sympathetic nerve in genetically spontaneously hypertensive rats. Methods and Results: We evaluated Treg cells in stroke-prone spontaneously hypertensive rats (SHRSP) at 3 week (early pre-hypertensive stage), 5 week (late pre-hypertensive stage), or 15 week (established hypertensive stage) old, and in age-matched normotensive Wistar-Kyoto rats (WKY). CD4+CD25+Foxp3+ cells (Treg cells) in the spleen and peripheral blood did not differ between WKY and early pre-hypertensive SHRSP, whereas significantly decreased both in late pre-hypertensive (%CD25+Foxp3+ gated on CD4+ cells in the spleen; 7.7±0.5 vs. 5.5±0.3, n=5 for each, p=0.0080, blood; 6.7±0.7 vs. 3.4±0.8, n=4 for each, p=0.0060) and established hypertensive SHRSP (spleen; 9.9±0.7 vs. 5.4±0.4, n=4 for each, p=0.0011, blood; 8.8±0.7 vs. 4.5±0.1, n=4 for each, p=0.0009). We performed splenic denervation (or sham operation) in SHRSP at prehypertensive stage. After 4 weeks of splenic denervation, splenic Treg cells were increased compared with sham-operated SHRSP (4.2±0.1 vs. 6.1±0.3, n=7 for each, p<0.0001). Furthermore, splenic denervation in SHRSP at prehypertensive stage delayed blood pressure elevation (n=7 for each, p<0.001, vs. sham-operated SHRSP), whereas splenectomy did not affect blood pressure. Conclusion: Our results indicate that splenic denervation attenuates the decrease in splenic Treg cells and delays the development of hypertension, suggesting that splenic sympathetic nerve and decrease in Treg cells play a key role in the onset of hypertension in SHRSP.